In 1849, the Damascene notable Mikha’il Mishaqa became an open convert to Protestantism. He also published an autobiographical account of his religious opinions, stating that since his youth he had not been a believer in any recognised religion, although outwardly conforming to the Greek Catholic rite of his family. What had initially provoked his religious crisis, around 1818, was his reading of European Enlightenment books translated into Arabic at Damietta. Mishaqa was apparently not alone. At a similar period Protestant missionaries were reporting on the dangers of groups of Syrian Christians falling prey to scepticism or unbelief; Catholic missionaries were also on their guard against the ‘modern errors’ emanating from Europe; and accounts of temptation into religious doubt began to appear in Arabic literary texts. This hitherto hidden facet of intellectual and religious life in Ottoman Syria calls into question the relations between new, European-derived ideas – of both ‘Enlightenment’ and Christian varieties – and existing intellectual trends in the Arab world. It also calls attention to contemporary shifts in the inter-religious dynamics of Syria, with the creation of the new millet regime and related conversions between religious communities. This paper will examine the possible meanings of unbelief in this context through a range of published sources and missionary archives, including previously unexamined correspondence between Protestant missionaries and converts such as Mikha’il Mishaqa. It argues that the threat of religious unbelief or scepticism was a key element in Protestant missionaries’ understanding of Syrian society, alongside their oppositional relationship to existing local forms of religion: Protestantism offered itself as a ‘middle way’ between the ‘superstition’ of established local churches and the ‘infidelity’ into which Syrian Christians were in danger of falling, particularly as they encountered the scientific and sceptical heritage deriving from the Enlightenment. The relationship between faith, doubt, and scientific or rational knowledge thus played a significant part in Arabic-speaking Syrians’ appropriations of Western knowledge from the first half of the nineteenth century onwards.